DESCRIPTION (provided by candidate): South Africa lies at the epicenter of both the HIV and TB epidemics, each fueling the other. AIDS is the leading cause of death in sub-Saharan Africa, and TB is the region's leading cause of HIV-related morbidity and mortality. Despite considerable data, the optimal strategy for TB diagnosis and prevention among HIV-infected patients in highly endemic, resource-limited settings remains unclear. Dr. Melissa A. Bender, guided by mentors Kenneth A. Freedberg, MD, MSc and C. Robert Horsburgh, MD, MUS will apply decision-analytic methods to evaluate different strategies for TB diagnosis and prevention in HIV-infected individuals. The four specific aims of this K01 proposal are: 1) To build a CD4- specific decision-analytic model of different strategies for diagnosis of subclinical TB in HIV-infected patients in South Africa;2) To determine the clinical and cost parameters associated with TB/HIV coinfection in South Africa, including the natural history of TB as well as TB relapse and reinfection rates;3) To use the model developed in Aim 1 and input parameters defined in Aim 2 to estimate clinical outcomes and costs associated with alternative strategies for TB diagnosis among HIV-infected individuals in South Africa;4) To develop a CD4-specific Markov model of HIV/TB coinfection to project survival, costs, and cost-effectiveness associated with alternative strategies for prevention of active TB in South Africa. The candidate is a junior faculty member in the Division of Infectious Diseases at Massachusetts General Hospital with a demonstrated commitment to improving infectious disease outcomes in resource-limited settings. She already has strong training in decision modeling methods, as well as a clear plan to develop the additional quantitative skills needed to apply a novel, CD4-specific approach to these critically important questions. Dr. Bender will benefit from the expertise of the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) group based at Harvard Medical School, and the mentorship of two senior investigators with exceptional track records of guiding young investigators toward productive and independent research careers. Completion of this research has the potential to add substantially to the current approach to TB diagnosis and prevention in the developing world.